Background
Physiologic functions of m6A modifications
Physiological activities | Genes involved | Description | Reference |
---|---|---|---|
Spermatogenesis | Plzf, Dnmt3b Id4 and Sohlh2 | Deletion of m6A results in the dysregulation of spermatogenesis | [39] |
T cell homeostasis | SOCS1, SOCS3 and CISH | Decreased m6A modification inhibits naive T cell proliferation and differentiation but maintains cell survival | [40] |
Drosophila sex determination | Sxl | YT521-B reads the m6A modification of Sxl to promote Sxl alternative splicing, which determines female physiognomy | [38] |
Heat shock response | Hsp105 | Under heat shock stress, m6A is preferentially deposited at the 5’UTR of new stress-inducible transcripts, such as Hsp105 (HSPH1), and enhances cap-independent translation initiation | [28] |
Somatic cell reprogramming and pluripotency of ESCs | Nanog, Sox2, Klf4 and c-Myc | High m6A modification levels accelerate mRNA degradation of these genes, which damages ESC self-renewal and somatic cell reprogramming | [37] |
m6A modulates spermatogenesis
m6A influences T cell homeostasis
m6A is involved in Drosophila sex determination
High levels of m6A during the heat shock response
m6A influences somatic cell reprogramming and maintains the pluripotency of embryonic stem cells (ESCs)
Aberrant m6A modification contributes to diversified tumours
Tumour Type | Gene involved | Gene function | Description | reference |
---|---|---|---|---|
Acute myeloid leukaemia | ASB2 RARA | Anti-oncogene | Elevated FTO leads to low levels of m6A on ASB2 and RARA at UTRs, which reduces the mRNA and protein levels of these two genes | [47] |
MYB MYC | Oncogene | METTL14 enhances m6A modification of MYB and MYC, which in turn leads to overexpression of MYB and MYC | [48] | |
BCL2 PTEN | Oncogene | Increased METTL3 in AML enhances m6A modification of BCL2 and PTEN, which leads to overexpression of BCL2 and PTEN | [50] | |
SP1 | Oncogene | METTL3 binds to the promoter region of sp1 and enhances m6A modification and gene expression | [51] | |
Hepatocellular carcinoma | SOCS2 | Anti-oncogene | High expression of METTL3 in human HCC leads to high m6A levels on SOCS2, causing the rapid degradation of SOCS2 | [60] |
microRNA126 | Anti-oncogene | Decreased METTL14 reduces m6A modification levels and the expression of microRNA126 | [61] | |
Glioblastoma stem cells | ADAM19 | Oncogene | Low levels of METTL3 and METTL14 decrease m6A modification of ADAM19, which enhances the expression of ADAM19 | [69] |
FOXM1 | Oncogene | High levels of ALKBH5 decrease m6A modification levels of FOXM1 and enhance the expression of FOXM1, which ultimately causes glioblastoma | [70] | |
Breast cancer | KLF4 NANOG | Oncogene | ZNF217 interacts with METTL3 and inhibits the m6A methylation of KLF4 and NANOG, which ultimately leads to high expression of KLF4 and NANOG | [74] |
HBXIP | Oncogene | High levels of METTL3 enhance m6A modification of HBXIP, which accelerates HBXIP expression | [75] | |
MAGI3 | Anti-oncogene | High levels of m6A modification in the large internal exon of MAGI3 promote the occurrence of breast cancer | [31] | |
Cervical cancer | β-catenin | Anti-oncogene | Upregulated FTO represses m6A modification of β-catenin and induces chemoradiotherapy resistance | [79] |